4-Thiazolidinone Derivatives as MMP Inhibitors in Tissue Damage: Synthesis, Biological Evaluation and Docking Studies.
Matteo IncertiLucia CrascíPaola ViciniEsin Aki YalcinIsmail YalcinTugba Ertan-BolelliVenera CardileAdriana Carol Eleonora GrazianoAnnamaria PanicoPublished in: Molecules (Basel, Switzerland) (2018)
Nine 2-(1,2-benzothiazol-3-yl)-N-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl)propanamides combining a benzisothiazole and 4-thiazolidinone in one framework were designed and synthesized. The aim of the study was to verify their effectiveness to affect the inflammatory/oxidative process in which free oxygen and nitrite (ROS and RNS) radicals, inflammatory mediators, such as nuclear factor κB (NF-κB), and matrix metalloproteinases (MMPs) are involved. Docking studies of all the compounds were performed in order to explore their binding mode at the MMP-9 protein. An appreciable anti-inflammatory/potential wound healing effects of the tested compounds was highlighted. Derivative 23, bearing a 4-carboxyphenyl substituent at C2 of the 4-thiazolidinone ring, exhibited the highest activity, being able to inhibit MMP-9 at nanomolar level(IC50 = 40 nM).
Keyphrases
- nuclear factor
- protein protein
- oxidative stress
- toll like receptor
- molecular dynamics
- cell migration
- molecular dynamics simulations
- anti inflammatory
- wound healing
- case control
- small molecule
- nitric oxide
- randomized controlled trial
- dna damage
- systematic review
- photodynamic therapy
- cell death
- binding protein
- inflammatory response
- reactive oxygen species
- lps induced
- cell proliferation
- risk assessment
- water soluble